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Receptor antagonist and selective agonist derivatives of mouse interleukin‐2
Mouse interleukin‐2 (mIL‐2) proteins with substitutions at two residues (D34 and Q141) that interact specifically with different signalling subunits (respectively, beta and gamma) of the IL‐2 receptor (IL‐2R) were examined using several in vitro cellular assays. Proteins with specific substitutions...
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Published in: | The EMBO journal 1992-11, Vol.11 (11), p.3905-3910 |
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Main Authors: | , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | Mouse interleukin‐2 (mIL‐2) proteins with substitutions at two residues (D34 and Q141) that interact specifically with different signalling subunits (respectively, beta and gamma) of the IL‐2 receptor (IL‐2R) were examined using several in vitro cellular assays. Proteins with specific substitutions at both residues were partial agonists and their maximal responses varied widely in different IL‐2‐responsive cell types. Two of these cell types had comparable numbers of IL‐2R and similar affinities for wild‐type mIL‐2 and mutant mIL‐2 proteins. However, the more responsive cell type had ‘spare’ IL‐2R. Various mIL‐2 proteins with substitutions at Q141 had modest defects in IL‐2R‐binding and were potent antagonists of native mIL‐2 action. Proteins with bulky or basic substitutions at residue D34 were weak antagonists due to severely reduced IL‐2 binding and their reduced binding paralleled their defects in IL‐2R activation. Our results suggest that interaction of mIL‐2 with IL‐2R beta is more important for binding than activation and that the converse holds for mIL‐2 interaction with IL‐2R gamma. Also genetic manipulation of the interaction of IL‐2 with IL‐2R beta and IL‐2R gamma has led to the discovery of potentially useful IL‐2 antagonists and selective agonists. |
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ISSN: | 0261-4189 1460-2075 |
DOI: | 10.1002/j.1460-2075.1992.tb05483.x |